Introduction: Stem cell transplantation is currently implemented clinically, but is limited by low retention and insufficient targeting to the injured heart. Platelets have the natural ability to home to injury and play an important in recruiting stem cells to the sites of injury on blood vessels.
Hypothesis: We seek to harness the natural injury-homing ability of platelets to enhance the vascular delivery of cardiac stem cells (CSCs) to myocardial infarction (MI) injury.
Methods: We fuse platelet nanovesicles (PNVs) onto the surface of CSCs to form engineered PNV-CSCs. This strategy is nontoxic to CSCs. The ability of PNV-CSCs for binding onto the injured vessel is tested ex vivo. Rat and pig models of ischemia/reperfusion are established to test PNV-CSCs.
Results: PNV-CSCs possessed surface markers of platelets, which are associated with platelet adhesion to injury sites. PNV-CSCs can selectively bind collagen-coated surface and denuded rat aorta ex vivo. In rats and pigs with ischemia/reperfusion injury, PNV decoration increases CSC retention in the heart and augments therapeutic benefits. PNV-CSCs treatment robustly boosts cardiac function with the highest left ventricular ejection fraction and best cardiac morphology by promoting angiomyogenesis.
Conclusions: The engineered PNV-CSCs possess the natural targeting and repairing ability of their parental cells: platelets and of CSCs. This method offers fast, straightforward, and safe manipulation of stem cells with no genetic alterations of the cells and is generalizable to multiple cell types.